This competing renewal application from the Hawaii Colorectal Cancer Family Registry for RFA CA-08-502 is to continue our participation in the NCI Colon Cancer Family Registry (Colon CFR). The Hawaii CFR site capitalizes on our unique access to understudied ethnic/racial minorities at high colorectal cancer (CRC) risk, and on characteristics of Hawaii's population that make it eminently suitable for epidemiologic research (geographic remoteness, stability, large pedigrees, population registries, good compliance) and our on-going research on diet, genetic variation and CRC in multiethnic populations. We have made good progress toward our aims with 588 population-based families recruited (including 342 Japanese American and 78 African American families), composed of 2,117 participants (588 CRC-affected probands, 172 CRC-affected relatives, 1,147 relatives and 210 spouse controls), as of October 30, 2007. We also have collected blood on 1,488 participants (buccal cells on an additional 52) and tumor blocks on 271 affected participants. We have established lymphoblastoid cell lines on all PHASE I probands and extracted genomic DMA for 1,299 subjects and tumor DMA for 205. We have completed passive follow-up on all participants and active follow-up on over 85% of eligible subjects. We have enhanced our local informatics system and transmitted data of very high quality to the CFR Informatics Center. We have participated in all Colon CFR-wide initiatives to enhance the resource, including testing tumors by microsatellite instability (MSI) and immunohistochemistry (IHC) for DNA mismatch repair (MMR) defect and testing for germ-line mutations in MLH1, MSH2, MSH6 and MYH for PHASE I samples. We have also enhanced the CFR data, especially with regard to diet and race/ethnicity. We have conducted pilot studies and are engaged in collaborative research with the CFR, with an emphasis on explaining the high CRC risk of Japanese Americans and African Americans (R01 CA104132), the role of chronic inflammation in CRC (R01 CA129063) and characterizing the 8q24 and 9p24 susceptibility loci in CRC. In this renewal (PHASE III), we will primarily maintain and enhance the infrastructure that we have established. We will maintain the informatics systems and biorepository, expand existing high-risk families, recruit a small number of new MMR or MYH mutation carrying or Amsterdam families, complete the molecular characterization (IHC, and MMR and MYH gene testing) of our cases and continue the follow-up on the existing families.